Liver disease is a major and growing public health concern. While many patients presenting with viral or alcoholic hepatitis will recover well, others will have significant progression of their disease (more than 50% of patients with exposure to hepatitis C become chronically infected), often initially without externally apparent symptoms. This can lead to the late development of frank liver cirrhosis, with its attendant potentially life-threatening complications, and an increased risk of developing hepatocellular carcinoma. While many patients can be successfully treated in the earlier stages of the disease, treatment is much less successful once full-blown cirrhosis has developed. However, the available treatments are not without their own cost and potential risks, and cannot be given routinely to all patients at their initial presentation. Thus, the ability to detect progression of liver disease at an earlier stage would enable more effective treatment and the prevention of later complications, while avoiding treatment of those patients who do not require it. Unfortunately, the currently available noninvasive means of detecting the early progression of the disease are limited in their accuracy, thus often leading to a need for repeated liver biopsies to follow those patients who are felt to be at a higher risk of developing cirrhosis. This proposed research is focused on the initial development and testing of a new method for the noninvasive evaluation of liver stiffness, based on tagged magnetic resonance imaging (tMRI), which is expected to provide a sensitive early marker for the development of liver fibrosis, an important hallmark of the progression toward cirrhosis. Cardiac motion produces transmitted motion in the liver that can be seen and measured with tMRI. Fibrosis of the liver has been seen to produce qualitative and quantitative changes in this liver motion in our initial results. The proposed research will develop improved tools to study the changes in this motion associated with liver fibrosis, and will correlate them with the degree of fibrosis as a means to validate the results. This new method for assessment of liver stiffness produces images that can be directly and intuitively understood;it can be implemented on conventional MRI systems, requiring only minor imaging software modification and the use of suitable software tools for analysis of the resulting images;and it can be rapidly carried out. These features all make it potentially suitable for incorporation in routine liver MRI evaluations when there is a question of possible increased liver stiffness. Thus, there is a significant potential for an important beneficial impact of this research on patient care. PUBLIC HEALTH RELEVANCE: Liver disease is an important and growing public health problem, with there frequently being clinically silent progression to the later serious complications of cirrhosis. However, conventional noninvasive methods of detecting liver fibrosis, a hallmark of developing cirrhosis, are unreliable, often resulting in the need for repeated liver biopsies (with their associated discomfort and risk) to follow patients at risk for progressive liver disease. The overall aim of this project is the development and evaluation of a new method for assessing the stiffness of the liver, specifically, the use of tagged magnetic resonance imaging (tMRI) to measure the motion and deformation induced in the liver by the motion of the heart;if successful, this could provide a way to avoid the need for biopsy in following many patients with liver disease.